CDH2

Cadherin 2, type 1, N-cadherin (neuronal)
	; PDB rendering based on 1ncg.
Available structures
PDB	PDBe, 1ncg, 1nch, 1nci, 1ncj
Identifiers
Symbols	CDH2; CD325; CDHN; CDw325; NCAD
External IDs	OMIM: 114020 MGI: 88355 HomoloGene: 20424 GeneCards: CDH2 Gene
Gene Ontology
Molecular function	• calcium ion binding; • protein binding; • beta-catenin binding; • protein kinase binding; • protein complex binding; • RPTP-like protein binding; • alpha-catenin binding; • gamma-catenin binding;
Cellular component	• plasma membrane; • plasma membrane; • cell-cell junction; • cell-cell adherens junction; • fascia adherens; • integral to membrane; • catenin complex; • lamellipodium; • synapse;
Biological process	• cell adhesion; • homophilic cell adhesion; • heterophilic cell-cell adhesion; • synapse assembly; • calcium-dependent cell-cell adhesion; • cell migration; • regulation of myelination; • regulation of protein localization; • cell junction assembly; • adherens junction organization; • regulation of Rho protein signal transduction; • muscle cell differentiation; • positive regulation of MAPKKK cascade; • cell-cell junction organization; • blood vessel morphogenesis; • regulation of axonogenesis; • striated muscle cell differentiation; • positive regulation of muscle cell differentiation; • protein heterooligomerization; • negative regulation of canonical Wnt receptor signaling pathway;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

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Cadherin-2 (CDH2), also known as neural cadherin (NCAD) is a protein that in humans is encoded by the CDH2 gene.^[1]^[2] CDH2 has also been designated as CD325 (cluster of differentiation 325).

[edit] Function

Cadherin 2 a classical cadherin from the cadherin superfamily. Cadherin 2 is a calcium dependent cell-cell adhesion glycoprotein comprising five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. The protein functions during gastrulation and is required for establishment of left-right asymmetry. At certain central nervous system synapses, presynaptic to postsynaptic adhesion is mediated at least in part by this gene product.^[3]

N-cadherins interact with catenins to play an important role in learning and memory (For full article see Cadherin-catenin complex in learning and memory).

[edit] Role in cancer metastasis

N-Cadherin is commonly found in cancer cells and provides a mechanism for transendothelial migration. When a cancer cell adheres to the endothelial cells of a blood vessel it up-regulates the src kinase pathway, which phosphorylates beta-catenins attached to both N-cadherin (this protein) and E-cadherins. This causes the intercellular connection between two adjacent endothelial cells to fail and allows the cancer cell to slip through.^[4]

[edit] Interactions

CDH2 has been shown to interact with Beta-catenin,^[5]^[6] Plakoglobin,^[5]^[7] Catenin (cadherin-associated protein), alpha 1,^[5]^[6] CTNND1,^[5]^[6] LRRC7,^[8] CDH11,^[5] and type IIb RPTPs including PTPRM.^[9]^[10]

[edit] References

^ Walsh FS, Barton CH, Putt W, Moore SE, Kelsell D, Spurr N, Goodfellow PN (September 1990). "N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene". J. Neurochem. 55 (3): 805–12. doi:10.1111/j.1471-4159.1990.tb04563.x. PMID 2384753.
^ Reid RA, Hemperly JJ (October 1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Res. 18 (19): 5896–5896. doi:10.1093/nar/18.19.5896. PMC 332345. PMID 2216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332345.
^ "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1000.
^ Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D (2009). "Multi-scale modelling of cancer cell intravasation: the role of cadherins in metastasis". Phys Biol 6 (1): 016008. doi:10.1088/1478-3975/6/1/016008. PMID 19321920.
^ ^a ^b ^c ^d ^e Straub, Beate K; Boda Judit, Kuhn Caecilia, Schnoelzer Martina, Korf Ulrike, Kempf Tore, Spring Herbert, Hatzfeld Mechthild, Franke Werner W (Dec. 2003). "A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells". J. Cell. Sci. (England) 116 (Pt 24): 4985–95. doi:10.1242/jcs.00815. ISSN 0021-9533. PMID 14625392.
^ ^a ^b ^c Wahl, James K; Kim Young J, Cullen Janet M, Johnson Keith R, Wheelock Margaret J (May. 2003). "N-cadherin-catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane". J. Biol. Chem. (United States) 278 (19): 17269–76. doi:10.1074/jbc.M211452200. ISSN 0021-9258. PMID 12604612.
^ Sacco, P A; McGranahan T M, Wheelock M J, Johnson K R (Aug. 1995). "Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin". J. Biol. Chem. (UNITED STATES) 270 (34): 20201–6. doi:10.1074/jbc.270.34.20201. ISSN 0021-9258. PMID 7650039.
^ Izawa, Ichiro; Nishizawa Miwako, Ohtakara Kazuhiro, Inagaki Masaki (Feb. 2002). "Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses". J. Biol. Chem. (United States) 277 (7): 5345–50. doi:10.1074/jbc.M110052200. ISSN 0021-9258. PMID 11729199.
^ Brady-Kalnay SM, Rimm DL, Tonks NK (1995). "Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo.". J Cell Biol 130 (4): 977–86. doi:10.1083/jcb.130.4.977. PMC 2199947. PMID 7642713. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2199947.
^ Brady-Kalnay SM, Mourton T, Nixon JP, Pietz GE, Kinch M, Chen H et al. (1998). "Dynamic interaction of PTPmu with multiple cadherins in vivo.". J Cell Biol 141 (1): 287–96. doi:10.1083/jcb.141.1.287. PMC 2132733. PMID 9531566. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132733.

[edit] Further reading

Doherty P, Smith P, Walsh FS (1997). "Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors". Perspectives on developmental neurobiology 4 (2–3): 157–68. PMID 9168198.
Makrigiannakis A, Coukos G, Blaschuk O, Coutifaris C (2000). "Follicular atresia and luteolysis. Evidence of a role for N-cadherin". Ann. N. Y. Acad. Sci. 900: 46–55. doi:10.1111/j.1749-6632.2000.tb06215.x. PMID 10818391.
Hazan RB et al. (2004). "Cadherin switch in tumor progression". Ann. N. Y. Acad. Sci. 1014: 155–63. doi:10.1196/annals.1294.016. PMID 15153430.
Cavallaro U (2005). "N-cadherin as an invasion promoter: a novel target for antitumor therapy?". Current opinion in investigational drugs (London, England : 2000) 5 (12): 1274–8. PMID 15648948.
Salomon D et al. (1992). "Extrajunctional distribution of N-cadherin in cultured human endothelial cells". J. Cell. Sci. 102 ( Pt 1): 7–17. PMID 1500442.
Knudsen KA, Wheelock MJ (1992). "Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin". J. Cell Biol. 118 (3): 671–9. doi:10.1083/jcb.118.3.671. PMC 2289540. PMID 1639850. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2289540.
Reid RA, Hemperly JJ (1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Res. 18 (19): 5896–5896. doi:10.1093/nar/18.19.5896. PMC 332345. PMID 2216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332345.
Walsh FS et al. (1990). "N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene". J. Neurochem. 55 (3): 805–12. doi:10.1111/j.1471-4159.1990.tb04563.x. PMID 2384753.
Selig S et al. (1995). "Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene". Proc. Natl. Acad. Sci. U.S.A. 92 (9): 3702–6. doi:10.1073/pnas.92.9.3702. PMC 42029. PMID 7731968. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42029.
Wallis J, Fox MF, Walsh FS (1994). "Structure of the human N-cadherin gene: YAC analysis and fine chromosomal mapping to 18q11.2". Genomics 22 (1): 172–9. doi:10.1006/geno.1994.1358. PMID 7959764.
Andersson AM, Edvardsen K, Skakkebaek NE (1995). "Expression and localization of N- and E-cadherin in the human testis and epididymis". Int. J. Androl. 17 (4): 174–80. doi:10.1111/j.1365-2605.1994.tb01239.x. PMID 7995652.
Matsuyoshi N, Imamura S (1997). "Multiple cadherins are expressed in human fibroblasts". Biochem. Biophys. Res. Commun. 235 (2): 355–8. doi:10.1006/bbrc.1997.6707. PMID 9199196.
Navarro P, Ruco L, Dejana E (1998). "Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization". J. Cell Biol. 140 (6): 1475–84. doi:10.1083/jcb.140.6.1475. PMC 2132661. PMID 9508779. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132661.
Gaidar YA, Lepekhin EA, Sheichetova GA, Witt M (1998). "Distribution of N-cadherin and NCAM in neurons and endocrine cells of the human embryonic and fetal gastroenteropancreatic system". Acta Histochem. 100 (1): 83–97. PMID 9542583.
Kremmidiotis G et al. (1998). "Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity". Genomics 49 (3): 467–71. doi:10.1006/geno.1998.5281. PMID 9615235.
Lu Q et al. (1999). "delta-catenin, an adhesive junction-associated protein that promotes cell scattering". J. Cell Biol. 144 (3): 519–32. doi:10.1083/jcb.144.3.519. PMC 2132907. PMID 9971746. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132907.
Shan WS et al. (2000). "Functional cis-heterodimers of N- and R-cadherins". J. Cell Biol. 148 (3): 579–90. doi:10.1083/jcb.148.3.579. PMC 2174798. PMID 10662782. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2174798.
Husi H et al. (2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nat. Neurosci. 3 (7): 661–9. doi:10.1038/76615. PMID 10862698.

[edit] External links

MeSH CDH2+protein,+human

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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[pmid2384753-0] Walsh FS, Barton CH, Putt W, Moore SE, Kelsell D, Spurr N, Goodfellow PN (September 1990). "N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene". J. Neurochem. 55 (3): 805–12. doi:10.1111/j.1471-4159.1990.tb04563.x. PMID 2384753.

[pmid2216790-1] Reid RA, Hemperly JJ (October 1990). "Human N-cadherin: nucleotide and deduced amino acid sequence". Nucleic Acids Res. 18 (19): 5896–5896. doi:10.1093/nar/18.19.5896. PMC 332345. PMID 2216790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=332345.

[2] "Entrez Gene: CDH2 cadherin 2, type 1, N-cadherin (neuronal)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1000.

[pmid19321920-3] Ramis-Conde I, Chaplain MA, Anderson AR, Drasdo D (2009). "Multi-scale modelling of cancer cell intravasation: the role of cadherins in metastasis". Phys Biol 6 (1): 016008. doi:10.1088/1478-3975/6/1/016008. PMID 19321920.

[pmid14625392-4] Straub, Beate K; Boda Judit, Kuhn Caecilia, Schnoelzer Martina, Korf Ulrike, Kempf Tore, Spring Herbert, Hatzfeld Mechthild, Franke Werner W (Dec. 2003). "A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells". J. Cell. Sci. (England) 116 (Pt 24): 4985–95. doi:10.1242/jcs.00815. ISSN 0021-9533. PMID 14625392.

[pmid12604612-5] Wahl, James K; Kim Young J, Cullen Janet M, Johnson Keith R, Wheelock Margaret J (May. 2003). "N-cadherin-catenin complexes form prior to cleavage of the proregion and transport to the plasma membrane". J. Biol. Chem. (United States) 278 (19): 17269–76. doi:10.1074/jbc.M211452200. ISSN 0021-9258. PMID 12604612.

[pmid7650039-6] Sacco, P A; McGranahan T M, Wheelock M J, Johnson K R (Aug. 1995). "Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin". J. Biol. Chem. (UNITED STATES) 270 (34): 20201–6. doi:10.1074/jbc.270.34.20201. ISSN 0021-9258. PMID 7650039.

[pmid11729199-7] Izawa, Ichiro; Nishizawa Miwako, Ohtakara Kazuhiro, Inagaki Masaki (Feb. 2002). "Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses". J. Biol. Chem. (United States) 277 (7): 5345–50. doi:10.1074/jbc.M110052200. ISSN 0021-9258. PMID 11729199.

[pmid7642713-8] Brady-Kalnay SM, Rimm DL, Tonks NK (1995). "Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo.". J Cell Biol 130 (4): 977–86. doi:10.1083/jcb.130.4.977. PMC 2199947. PMID 7642713. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2199947.

[pmid9531566-9] Brady-Kalnay SM, Mourton T, Nixon JP, Pietz GE, Kinch M, Chen H et al. (1998). "Dynamic interaction of PTPmu with multiple cadherins in vivo.". J Cell Biol 141 (1): 287–96. doi:10.1083/jcb.141.1.287. PMC 2132733. PMID 9531566. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132733.

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CDH2

Contents

[edit] Function

[edit] Role in cancer metastasis

[edit] Interactions

[edit] References

[edit] Further reading

[edit] External links

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